Metal Transport and Metallochaperones

Intracellular distribution of essential transition metals is mediated by specific metallochaperones and transporters localized in endomembranes. In other words, the major processes involved in hyperaccumulation of trace metals from the contaminated medium to the shoots by hyperaccumulators as proposed by Yang et al. (2005) include bioactivation of metals in the rhizosphere through root-microbial interaction enhanced uptake by metal transporters in the plasma membranes detoxification of metals by distributing metals to the apoplasts such as binding to cell walls and chelation of metals in the cytoplasm with various ligands (such as PCs, metallothioneins, metal-binding proteins) and sequestration of metals into the vacuole by tonoplast-located transporters. 

The last decade has seen an explosion of interest in Mn transport and regulation. While this remains poorly characterized in comparison with the much better studied areas of Fe and Cu homeostasis (see Metallochaperones Metal Ion Homeostasis), the basic principles of Mn metabolism are beginning to be worked out. In yeast, there are at least two independent systems for importing Mn into the cell. The high-affinity transporter, operative under... 

A number of bacterial metal transporters belong to the family of ATP-binding cassette (ABC) transporter system (see Metallochaperones Metal Ion Homeostasis) These systems constitute one of the most abundant superfamilies of proteins. They are involved in the transport of a wide variety of substances and in many cellular processes. The zinc transporter ZnuA from E. Coli and Synechocystis sp. 6803, the proposed zinc transporter TroA from Treponema pallidum, and the proposed manganese transporter Streptococcus pneumoniae surface antigen, PsaA, are placed in cluster 9 of the ABC transporters. ... 

The proteins that require metal ions as cofactors are numerous and are assorted in diverse cellular locations. How is it that these vastly different proteins all acquire their paitner metal ion in an accurate and efficient manner The process is quite complex and involves the cooperation of membrane transporters and metal carrying metallochaperones. 

In addition to the membrane bound transporters, the delivery of certain metals to their cognate metalloprotein involves the action of highly specific metal chaperone or metallochaperone proteins. These metal carriers are often soluble, as opposed to membrane associated, and act to directly insert the metal into the proper site of the metalloprotein. 

There are at least 100 Zn(II)-metalloproteins in E. coli 10), and if intracellular Zn(II) transport is similar to metal transport for other metal ions (24), then there must be at least 100 distinct Zn(II)-metallochaperones. The inability to identify even one Zn(II)-metallochaperone candidate argues against... 

Intracellular transport of metal ions has been a very well studied research area in the last few years. The most often-cited case of this transport involves copper transport in yeast by the copper metallochaperones 24, 25). Cu(I) enters the cytoplasm of yeast via copper transport receptors, and Cu(I) is bound by one of three transport proteins Lys7, Atxl, or Cox 17. Lys7 delivers copper to CuZn superoxide dismutase, Atxl delivers copper to ccc2 that activates an Fe(II) uptake system, and Cox 17 delivers copper to the mitochondria for the ultimate uptake into cytochrome c oxidase. A similar copper transport system has been reported in humans (26), and there may be a system in bacteria as well (27). Metal ion transport systems are known for iron, nickel, and manganese 24, 25, 28). However, no cytoplasmic Zn(II) transporters have been identified in... 

The third hypothesis for Zn(II) transport/homeostasis involves the presence of soluble, cytoplasmic Zn(II)-metallochaperones. In this model, Zn(II) is brought into the cytoplasm by Zn(II) transporters (ZnuABC, ZupT, PitA), binds to chaperone proteins/peptides, and thus distributes to the places in the cell where Zn(II) is needed. The total cytoplasmic concentration of free Zn(II) would remain at equilibrium values. This mechanism requires specific, intracellular metal ion transporters, such as the transporters (metallochaperones) that are known for Cu, Mn, and Fe delivery 24, 25, 28). While, no such cytoplasmic Zn(II)-metallochaperones have been identified in any organism, several groups have hypothesized their existence in eukaryotes and prokaryotes 3, 4, 9, 39). In this work, we conducted experiments in an effort to identify Zn(II)-metallochaperones in E. coli. 

Our understanding of Zn(II) homeostasis in E. coli is far from complete. It is clear that intracellular Zn(II) transport in bacteria is different that the transport of other metal ions, since none of the known Zn(II) proteins have the genes for transport proteins on the same operon/gene cluster. In addition, DNA microarrays have failed to identify a single Zn(II)-metallochaperone candidate. It is possible that Zn(II)-metallochaperones are not Zn(II)-responsive, and therefore would not be up- or down-regulated by the presence/absence of Zn(II). 

---